Transcatheter arterial chemoembolization combined with PD-1 inhibitors and Lenvatinib for hepatocellular carcinoma with portal vein tumor thrombus

BACKGROUND Hepatocellular carcinoma(HCC)patients complicated with portal vein tumor thrombus(PVTT)exhibit poor prognoses and treatment responses.AIM To investigate efficacies and safety of the combination of PD-1 inhibitor,transcatheter arterial chemoembolization(TACE)and Lenvatinib in HCC subjects comorbid with PVTT.METHODS From January 2019 to December 2020,HCC patients with PVTT types Ⅰ-Ⅳ were retrospectively enrolled at Beijing Ditan Hospital.They were distributed to either the PTL or TACE/Lenvatinib(TL)group.The median progression-free survival(mPFS)was set as the primary endpoint,while parameters like median overall survival,objective response rate,disease control rate(DCR),and toxicity level served as secondary endpoints.RESULTS Forty-one eligible patients were finally recruited for this study and divided into the PTL(n=18)and TL(n=23)groups.For a median follow-up of 21.8 months,the DCRs were 88.9%and 60.9%in the PTL and TL groups(P=0.046),res-pectively.Moreover,mPFS indicated significant improvement(HR=0.25;P<0.001)in PTL-treated patients(5.4 months)compared to TL-treated(2.7 months)patients.There were no treatment-related deaths or differences in adverse events in either group.CONCLUSION A triplet regimen of PTL was safe and well-tolerated as well as exhibited favorable efficacy over the TL regimen for advanced-stage HCC patients with PVTT types Ⅰ-Ⅳ.

Nomogram predicting the prognosis of primary liver cancer after radiofrequency ablation combined with transcatheter arterial chemoembolization

BACKGROUND The incidence and mortality rates of primary hepatocellular carcinoma(HCC)are high,and the conventional treatment is radiofrequency ablation(RFA)with transcatheter arterial chemoembolization(TACE);however,the 3-year survival rate is still low.Further,there are no visual methods to effectively predict their prognosis.AIM To explore the factors influencing the prognosis of HCC after RFA and TACE and develop a nomogram prediction model.METHODS Clinical and follow-up information of 150 patients with HCC treated using RFA and TACE in the Hangzhou Linping Hospital of Traditional Chinese Medicine from May 2020 to December 2022 was retrospectively collected and recorded.We examined their prognostic factors using multivariate logistic regression and created a nomogram prognosis prediction model using the R software(version 4.1.2).Internal verification was performed using the bootstrapping technique.The prognostic efficacy of the nomogram prediction model was evaluated using the concordance index(CI),calibration curve,and receiver operating characteristic RESULTS Of the 150 patients treated with RFA and TACE,92(61.33%)developed recurrence and metastasis.Logistic regression analysis identified six variables,and a predictive model was created.The internal validation results of the model showed a CI of 0.882.The correction curve trend of the prognosis prediction model was always near the diagonal,and the mean absolute error before and after internal validation was 0.021.The area under the curve of the prediction model after internal verification was 0.882[95%confidence interval(95%CI):0.820-0.945],with a specificity of 0.828 and sensitivity of 0.656.According to the Hosmer-Lemeshow test,χ^(2)=3.552 and P=0.895.The predictive model demonstrated a satisfactory calibration,and the decision curve analysis demonstrated its clinical applicability.CONCLUSION The prognosis of patients with HCC after RFA and TACE is affected by several factors.The developed prediction model based on the influencing parameters shows a good prognosis predictive efficacy.

Influence of transcatheter arterial embolization on symptom distress and fatigue in liver cancer patients

BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent malignancy,and transcatheter arterial embolization(TAE)has emerged as a pivotal therapeutic modality.How-ever,TAE may induce symptom distress and fatigue,adversely affecting the quality of life of patients.AIM To investigate symptom distress,fatigue,and associated factors in HCC patients undergoing TAE.METHODS We used a cross-sectional design and purposive sampling to enroll HCC patients who underwent TAE at our institution from January to December 2022.Question-naires were utilized to collect data on symptom distress and fatigue scores from the first to the third day after TAE.RESULTS Our study revealed a significant reduction in fatigue and symptom distress among patients after TAE.Pain,fatigue,insomnia,fever and abdominal dis-tension were the most common symptoms troubling patients during the first 3 d post-TAE.Marital status,presence of family support,physical functional status,age,and symptom distress were identified as predictors of fatigue in patients.CONCLUSION Healthcare professionals should educate HCC patients on symptom distress and INTRODUCTION Hepatocellular carcinoma(HCC)ranks as the fifth most prevalent cancer and the third leading cause of cancer-related mortality globally.Surgical intervention remains the cornerstone of HCC treatment;however,due to the challenges associated with early diagnosis and the lack of specific diagnostic markers,a considerable proportion of patients are diagnosed at advanced stages,rendering them ineligible for surgical interventions.Transcatheter arterial embolization(TAE)is an interventional therapeutic approach involving the insertion of a fine catheter via the femoral artery to reach the vasculature near the tumor site.TAE aims to obstruct the arterial supply to the tumor by deploying embolic agents,thereby inducing necrosis in cancer cells.This procedure is suitable for patients with good liver function and overall health,particularly those with large HCCs that have not invaded the portal vein[1,2].Nonetheless,following TAE,hepatocytes incur variable degrees of damage,leading to the development of a constel-lation of symptoms reminiscent of acute hepatitis.These symptoms include fatigue and systemic discomfort,such as nausea,vomiting,fever,abdominal pain,as well as transient elevations in aspartate aminotransferase(AST)and alanine aminotransferase(ALT),collectively referred to as postembolization syndrome[3,4].These symptoms may arise due to ischemia of the liver and gallbladder,temporary liver enlargement,and peritoneal irritation.While many studies have explored fatigue and symptom distress in cancer patients both nationally and internationally,with some focusing on symptom distress following transcatheter arterial chemoembolization,there has been limited in-depth investigation into the fatigue and symptom distress resulting from TAE treatment[5-8].Fatigue and pain are both subjective experiences,typically arising from the gradual depletion of energy reserves during the course of illness[9].Fatigue is particularly prevalent among cancer patients,with rates soaring as high as 90%.Despite extensive research exploring cancer-related fatigue and its influencing factors,a unanimous consensus remains elusive.Hence,the primary objective of this study was to investigate the symptom distress and fatigue experienced by liver cancer patients following TAE treatment and to analyze potential contributing factors.

Liver abscess and tracheal fistula induced by transcatheter arterial chemoembolization for hepatocellular carcinoma:A case report

BACKGROUND Transarterial chemoembolization(TACE)is a standard treatment for intermediate-stage hepatocellular carcinoma(HCC).The complications of TACE include biliary tract infection,liver dysfunction,tumor lysis syndrome,biloma,partial intestinal obstruction,cerebral lipiodol embolism,etc.There are few reports about tracheal fistula induced by TACE.CASE SUMMARY A 42-year-old man came to our hospital with cough and expectoration for 1 month after TACE for HCC.Laboratory test results showed abnormalities of albumin,hemoglobin,prothrombin time,C-reactive protein,D-dimer,and prothrombin.Culture of both phlegm and liver pus revealed growth of Citrobacter flavescens.Computed tomography showed infection in the inferior lobe of the right lung and a low-density lesion with gas in the right liver.Liver ultrasound showed that there was a big hypoechoic liquid lesion without blood flow signal.Drainage for liver abscess by needle puncture under ultrasonic guidance was performed.After 1 month of drainage and anti-infection therapy,the abscess in the liver and the infection in the lung were reduced obviously,and the symptom of expectoration was relieved.CONCLUSION Clinicians should be alert to the possibility of complications of liver abscess and tracheal fistula after TACE for HCC.Drainage for liver abscess by needle puncture under ultrasonic guidance could relieve the liver abscess and tracheal fistula.

Omics-imaging signature-based nomogram to predict the progression-free survival of patients with hepatocellular carcinoma after transcatheter arterial chemoembolization

BACKGROUND Enhanced magnetic resonance imaging(MRI)is widely used in the diagnosis,treatment and prognosis of hepatocellular carcinoma(HCC),but it can not effectively reflect the heterogeneity within the tumor and evaluate the effect after treatment.Preoperative imaging analysis of voxel changes can effectively reflect the internal heterogeneity of the tumor and evaluate the progression-free survival(PFS).AIM To predict the PFS of patients with HCC before operation by building a model with enhanced MRI images.METHODS Delineate the regions of interest(ROI)in arterial phase,portal venous phase and delayed phase of enhanced MRI.After extracting the combinatorial features of ROI,the features are fused to obtain deep learning radiomics(DLR)_Sig.DeLong's test was used to evaluate the diagnostic performance of different typological features.K-M analysis was applied to assess PFS in different risk groups,and the discriminative ability of the model was evaluated using the Cindex.RESULTS Tumor diameter and diolame were independent factors influencing the prognosis of PFS.Delong's test revealed multi-phase combined radiomic features had significantly greater area under the curve values than did those of the individual phases(P<0.05).In deep transfer learning(DTL)and DLR,significant differences were observed between the multi-phase and individual phases feature sets(P<0.05).K-M survival analysis revealed a median survival time of high risk group and low risk group was 12.8 and 14.2 months,respectively,and the predicted probabilities of 6 months,1 year and 2 years were 92%,60%,40%and 98%,90%,73%,respectively.The C-index was 0.764,indicating relatively good consistency between the predicted and observed results.DTL and DLR have higher predictive value for 2-year PFS in nomogram.CONCLUSION Based on the multi-temporal characteristics of enhanced MRI and the constructed Nomograph,it provides a new strategy for predicting the PFS of transarterial chemoembolization treatment of HCC.

Radiofrequency ablation combined with transcatheter arterial chemoembolization for recurrent liver cancer

BACKGROUND The recurrence rate of liver cancer after surgery is high.Radiofrequency ablation(RFA)combined with transcatheter arterial chemoembolization(TACE)is an effective treatment for liver cancer;however,its efficacy in recurrent liver cancer remains unclear.AIM To investigate the clinical effect of TACE combined with RFA in the treatment of recurrent liver cancer.METHODS Ninety patients with recurrent liver cancer were divided into 2 groups according to treatment plan:Control(RFA alone);and experimental[TACE combined with RFA(TACE+RFA)].The incidence of increased alanine aminotransferase levels,complications,and other indices were compared between the two groups before and after the procedures.RESULTS One month after the procedures,the short-term efficacy rate and Karnofsky Performance Status scores of the experimental group were significantly higher than those of the control group(P<0.05).Alpha-fetoprotein(AFP)and total bilirubin levels were lower than those in the control group(P<0.05);The overall response rate was 82.22%and 66.67%in the experimental and control groups,respectively;The disease control rate was 93.33%and 82.22%in the experimental and control groups,respectively,the differences are statistically significant(P<0.05).And there were no statistical differences in complications between the two groups(P>0.05).CONCLUSION TACE+RFA was effective for the treatment of recurrent liver cancer and significantly reduced AFP levels and improved various indices of liver function.

Identification of the key genes and mechanisms associated with transcatheter arterial chemoembolisation refractoriness in hepatocellular carcinoma

BACKGROUND Transcatheter arterial embolisation(TACE)is the primary treatment for intermediate-stage hepatocellular carcinoma(HCC)patients while some HCC cases have shown resistance to TACE.AIM To investigate the key genes and potential mechanisms correlated with TACE refractoriness in HCC.METHODS The microarray datasets of TACE-treated HCC tissues,HCC and non-HCC tissues were collected by searching multiple public databases.The respective differentially expressed genes(DEGs)were attained via limma R package.Weighted gene co-expression network analysis was employed for identifying the significant modules related to TACE non-response.TACE refractoriness-related genes were obtained by intersecting up-regulated TACE-associated and HCC-associated DEGs together with the genes in significant modules related to TACE nonresponse.The key genes expression in the above two pairs of samples was compared respectively via Wilcoxon tests and standard mean differences model.The prognostic value of the key genes was evaluated by Kaplan-Meier curve.Multivariate analysis was utilised to investigate the independent prognostic factor in key genes.Single-cell RNA(scRNA)sequencing analysis was conducted to explore the cell types in HCC.TACE refractoriness-related genes activity was calculated via AUCell packages.The CellChat R package was used for the investigation of the cell–cell communication between the identified cell types.RESULTS HCC tissues of TACE non-responders(n=66)and TACE responders(n=81),HCC(n=3941)and non-HCC(n=3443)tissues were obtained.The five key genes,DLG associated protein 5(DLGAP5),Kinesin family member 20A(KIF20A),Assembly factor for spindle microtubules(ASPM),Kinesin family member 11(KIF11)and TPX2 microtubule nucleation factor(TPX2)in TACE refractoriness-related genes,were identified.The five key genes were all up-regulated in the TACE non-responders group and the HCC group.High expression of the five key genes predicted poor prognosis in HCC.Among the key genes,TPX2 was an independent prognostic factor.Four cell types,hepatocytes,embryonic stem cells,T cells and B cells,were identified in the HCC tissues.The TACE refractoriness-related genes expressed primarily in hepatocytes and embryonic stem cells.Hepatocytes,as the providers of ligands,had the strongest interaction with embryonic stem cells that provided receptors.CONCLUSION Five key genes(DLGAP5,KIF20A,ASPM,KIF11 and TPX2)were identified as promoting refractory TACE.Hepatocytes and embryonic stem cells were likely to boost TACE refractoriness.

Pain management in patients with hepatocellular carcinoma after transcatheter arterial chemoembolisation: A retrospective study

BACKGROUND Pain after transcatheter arterial chemoembolisation(TACE)can seriously affect the prognosis of patients and the insertion of additional medical resources.AIM To develop an early warning model for predicting pain after TACE to enable the implementation of preventive analgesic measures.METHODS We retrospectively collected the clinical data of 857 patients(from January 2016 to January 2020)and prospectively enrolled 368 patients(from February 2020 to October 2022;as verification cohort)with hepatocellular carcinoma(HCC)who received TACE in the Hepatic Surgery Center of Tongji Hospital.Five predictive models were established using machine learning algorithms,namely,random forest model(RFM),support vector machine model,artificial neural network model,naive Bayes model and decision tree model.The efficacy of these models in predicting postoperative pain was evaluated through receiver operating characteristic curve analysis,decision curve analysis and clinical impact curve analysis.RESULTS A total of 24 candidate variables were included in the predictive models using the iterative algorithms.Age,preoperative pain,number of embolised tumours,distance from the liver capsule,dosage of iodised oil and preoperative prothrombin activity were closely associated with postoperative pain.The accuracy of the predictive model was compared between the training[area under the curve(AUC)=0.798;95%confidence interval(CI):0.745-0.851]and verification(AUC=0.871;95%CI:0.818-0.924)cohorts,with RFM having the best predictive efficiency(training cohort:AUC=0.869,95%CI:0.816-0.922;internal verification cohort:AUC=0.871;95%CI:0.818-0.924).CONCLUSION The five predictive models based on advanced machine learning algorithms,especially RFM,can accurately predict the risk of pain after TACE in patients with HCC.RFM can be used to assess the risk of pain for facilitating preventive treatment and improving the prognosis.

Percutaneous microwave ablation and transcatheter arterial chemoembolization for serum tumor markers and prognostics of middle-late primary hepatic carcinoma

BACKGROUND Primary hepatic carcinoma(PHC)has an insidious onset and is usually diagnosed in the middle and late stages.Although transcatheter arterial chemoembolization(TACE)is the preferred option for treating middle-and advanced-stage PHC,it has limited efficacy in killing tumor cells and poor long-term efficacy.TACE plus percutaneous microwave coagulation therapy(PMCT)is more effective than interventional therapy alone and can improve survival time.However,there are few reports on the effects of TACE and PMCT on serum marker levels and the prognosis of patients with advanced PHC.AIM To investigate the effect of PMCT+TACE on serum tumor markers and the prognosis of middle-late PHC.METHODS This retrospective study included 150 patients with middle-late PHC admitted to Zhongshan People’s Hospital between March 2018 and February 2021.Patients were divided into a single group(treated with TACE,n=75)and a combined group(treated with TACE+PMCT,n=75).Before and after treatment,the clinical efficacy and serum tumor marker levels[carbohydrate antigen 19-9(CA19-9),alpha-fetoprotein(AFP),and carcinoembryonic antigen(CEA)]of both groups were observed.The 1-year survival rates and prognostic factors of the two groups were analyzed.RESULTS The combined group had 21 and 35 cases of complete remission(CR)and partial remission(PR),respectively.The single group had 13 and 25 cases of CR and PR,decreased,with the decrease in the combined group being more significant(P<0.05).The 1-year survival rate of the combined group(80.00%)was higher than that of the single group(60.00%)(P<0.05).The average survival time within 1 year in the combined group was 299.38±61.13 d,longer than that in the single group(214.41±72.97 d,P<0.05).COX analysis revealed that tumor diameter,tumor number,and the treatment method were prognostic factors for patients with middle-late PHC(P<0.05).CONCLUSION TACE+PMCT is effective in treating patients with mid-late PHC.It reduces the levels of tumor markers,prolongs survival,and improves prognosis.

Clinical Analysis of Transcatheter Arterial Chemoembolization Sequential Microwave Ablation Combined with Targeted Therapy and Immunotherapy in the Treatment of Large Hepatocellular Carcinoma

Objective: To investigate the safety and efficacy of Transcatheter Arterial Chemoembolization (TACE), sequential Microwave Ablation (MWA) combined with targeted therapy and immunotherapy versus TACE combined with targeted therapy and immunotherapy in the treatment of large hepatocellular carcinoma (defined as tumor diameter > 5 cm). Methods: The prospective cohort study was conducted, with 81 patients with large hepatocellular carcinoma who were admitted to Jingzhou Central Hospital from 2018 to 2022, they were divided into two groups, 41 patients received TACE sequential MWA combined with targeted therapy and immunotherapy (observation group), and 40 patients received single TACE combined with targeted therapy and immunotherapy (control group). The short-term efficacies after 3 months of treatment, the Disease Control Rate (DCR), the Overall Survival (OS), adverse drug reactions and complications were compared and analyzed between the two groups. Results: The Objective Response Rate (ORR) of the observation group was significantly higher than that of the control group (ORR: 85.4% vs 57.5%, P = 0.005), The median Progression-Free Survival (PFS) and median OS of the observation group were better than those of the control group (mPFS: 16 months vs 10 months, P = 0.004;mOS: 39 months. vs 24 months, P = 0.008). The 1-, 2- and 3-year progression-free survival rates of the observation group were 72.9%, 50.4%, and 25.6%, and those of the control group were 30.4%, 11.0%, and 3.7%. The 1-, 2- and 3-year overall survival rates of the observation group were 78.9%, 71.7%, and 65.2%, and those of the control group were 65.1%, versus 42.1% and 36.9%. There was no significant difference in the incidence of adverse drug reactions and complications between the two groups. In this study, the adverse drug reactions were mild in Grades 1 - 2. Conclusion: TACE sequential MWA combined with targeted therapy and immunotherapy has efficacy and safety.

Usefulness of transcatheter arterial embolization for eighty-three patients with secondary postpartum hemorrhage:Focusing on difference in angiographic findings

BACKGROUND Transcatheter arterial embolization(TAE)has been widely used as an effective and a safe treatment method and was often used as an alternative to the surgical management,but there are limited studies on the efficacy and the safety for patients undergoing their secondary postpartum hemorrhage(PPH).AIM To evaluate the usefulness of TAE for secondary PPH focusing on the angiographic findings.METHODS We conducted a research from January 2008 to July 2022 on all 83 patients(mean:32 years,range:24-43 years)presented with secondary PPH and they were treated with TAE in two university hospitals.The medical records and angiography were retrospective reviewed in order to evaluate the patients’characteristics,delivery details,clinical status and peri-embolization management,angiography and embolization details,technical/clinical success and complications.The group with active bleeding sign and the group without it were also compared and analyzed.RESULTS On angiography,46(55.4%)patients showed active bleeding signs such as contrast extravasation(n=37)or pseudoaneurysm(n=8)or both(n=1),and 37(44.6%)patients showed non-active bleeding signs such as only spastic uterine artery(n=2)or hyperemia(n=35).In the active bleeding sign group there were more multiparous patients,low platelet count,prothrombin time prolongation,and high transfusion requirements.The technical success rates were 97.8%(45/46)in active bleeding sign group and 91.9%(34/37)in non-active bleeding sign group,and the overall clinical success rates were 95.7%(44/46)and 97.3%(36/37).An uterine rupture with peritonitis and abscess formation occurred to one patient after the embolization,therefore hysterostomy and retained placenta removal were performed which was a major complication.CONCLUSION TAE is an effective and a safe treatment method for controlling secondary PPH regardless of angiographic findings.

Pancreatic arteriovenous malformation treated with transcatheter arterial embolization:Two case reports and review of literature

BACKGROUND Various treatment methods are available for the treatment of pancreatic arteriovenous malformation(P-AVM);however,there are no established treatment options for asymptomatic P-AVM.CASE SUMMARY A 47-year-old and a 50-year-old male patients sought treatment for P-AVM in the pancreas,which was incidentally detected during routine abdominal computed tomography and magnetic resonance imaging conducted as part of a health check-up.They underwent transcatheter arterial embolization(TAE),and over the course of a 9-year follow-up period,the AVM did not worsen and was asymptomatic.CONCLUSION TAE can be considered as an alternative treatment option for P-AVM in selective cases where patients are asymptomatic or have a high surgical risk.

Transcatheter arterial chemoembolization followed by immediate radiofrequency ablation for large solitary hepatocellular carcinomas

AIM: To assess the technical safety and efficacy of transcatheter arterial chemoembolization (TACE) combined with immediate radiofrequency ablation (RFA) for large hepatocellular carcinomas (HCC) (maximum diameter ≥ 5 cm). METHODS: Individual lesions in 18 patients with HCCs (mean maximum diameter: 7.5 cm; range: 5.1-15.5 cm) were treated by TACE combined with percutaneous RFA between January 2010 and June 2012. All of the patients had previously undergone one to four cycles of TACE treatment. Regular imaging and laboratory tests were performed to evaluate the rate of technical success, technique-related complications, local-regional tumor responses, recurrence-free survival time and survival rate after treatment.RESULTS: Technical success was achieved for all 18 visible HCCs. Complete response (CR) was observed in 17 cases, and partial response was observed in 1 case 1 mo after intervention. The CR rate was 94.4%. Local tumors were mainly characterized by coagulative necrosis. During follow-up (2-29 mo), the mean recurrencefree survival time was 16.8 ± 4.0 mo in 17 cases of CR. The estimated overall survival rate at 6, 12, and 18 mo was 100%. No major complications were observed. Levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the blood of 17 patients transiently increased on the third day after treatment (ALT 200.4 ± 63.4 U/L vs 24.7 ± 9.3 U/L, P < 0.05; AST 228.1 ± 25.4 U/L vs 32.7 ± 6.8 U/L, P < 0.05). Severe pain occurred in three patients, which was controlled with morphine and fentanyl. CONCLUSION: TACE combined with immediate RFA is a safe and effective treatment for large solitary HCCs. Severe pain is a major side effect, but can be controlled by morphine.

Balloon-occluded transcatheter arterial chemoembolization for hepatocellular carcinoma

Transcatheter arterial chemoembolization(TACE) is widely accepted as a treatment for patients with hepatocellular carcinoma(HCC) in the intermediate stage according to the Barcelona Clinic Liver Cancer(BCLC) guidelines. Recently, balloon-occluded TACE(B-TACE) was developed in Japan. Despite the lack of a clear definition, B-TACE is generally defined as the infusion of emulsion of chemotherapeutic agents with lipiodol followed by gelatin particles under the occlusion of feeding arteries by a microballoon catheter, which leads to the dense lipiodol emulsion(LE) accumulation in HCC nodules. This phenomenon cannot be explained only by the prevention of proximal migration and leakage of embolization materials; it further involves causing local changes in the hemodynamics of the surrounding occlusion artery and targeted HCC nodules. Balloon-occluded arterial stump pressure plays an important role in the dense LE accumulation in targeted HCC nodules. Although randomized controlled trials comparing the therapeutic effect and the prognosis of B-TACE to those of the other TACE procedures, such as conventional-TACE and drug-eluting beads TACE, are still lacking, B-TACE is thought to be a promising treatment. The purpose of this review is to summarize the mechanism, therapeutic effect, indication, prognosis and complications of BTACE.

Efficacy of postoperative adjuvant transcatheter arterial chemoembolization in hepatocellular carcinoma patients with microvascular invasion

AIM To investigate the efficacy and safety of postoperative adjuvant transcatheter arterial chemoembolization(PA-TACE) in preventing tumor recurrence and improving survival in Barcelona Clinic Liver Cancer(BCLC) early(A) and intermediate(B) stage hepatocellular carcinoma(HCC) patients with microvascular invasion(MVI).METHODS A total of 519 BCLC A or B HCC patients treated by liver resection alone or followed by PA-TACE between January 2012 and December 2015 were studied retrospectively. Univariate and multivariate analyses were performed to investigate the risk factors for recurrence-free survival(RFS) and overall survival(OS). Multiple logistic regression was used to identify the clinicopathological characteristics associated with MVI. The rates of RFS and OS were compared among patients with or without MVI treated with liver resection alone or followed by PA-TACE. RESULTS Univariate and multivariate analyses demonstrated that serum AFP level > 400 ng/m L, tumor size > 5 cm, tumor capsule invasion, MVI, and major hepatectomy were risk factors for poor OS. Tumor capsule invasion, MVI, tumor size > 5 cm, HBV-DNA copies > 1 x 104 IU/m L, and multinodularity were risk factors for poor RFS. Multiple logistic regression identified serum AFP level > 400 ng/m L, tumor size > 5 cm, and tumor capsule invasion as independent predictors of MVI. Both OS and DFS were significantly improved in patients with MVI who received PA-TACE as compared to those who underwent liver resection alone. Patients without MVI did not show a significant difference in OS and RFS between those treated by liver resection alone or followed by PA-TACE.CONCLUSION PA-TACE is a safe adjuvant intervention and can efficiently prevent tumor recurrence and improve the survival of BCLC early-and intermediate-stage HCC patients with MVI.

Association between vascular endothelial growth factor and metastasis after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma

BACKGROUND: Hypoxia up-regulates vascular endothelialgrowth factor (VEGF) and stimulates the growth of hepa-tocellular carcinoma (HCC) cells. This study was designedto investigate the association between changes in plasmaVEGF levels after transcatheter arterial chemoembolization(TACE) and HCC progression, especially in relation tometastasis.METHODS: Plasma VEGF levels were measured by quati-tative sandwich enzyme-linked immunosorbent assay(ELISA R&D system). Plasma VEGF levels were measuredbefore, 3 days and 4 weeks after TACE in 30 patients withHCC. The development of metastasis was evaluated at theend of the third month after TACE.RESULTS: The plasma VEGF levels of the 30 patients withHCC were 154.47±90.17 pg/ml. The total plasma VEGFlevels after TACE increased compared with their basal levels(P<0.05), and the plasma VEGF levels had a tendency toincrease in patients with heterogenous uptake of iodizdoiland portal vein thrombosis. Follow-up for six monthsshowed metastatic foci in 20 patients (74%) with increasedplasma VEGF, but none of the patients with decreased plas-ma VEGF developed metastasis.CONCLUSION: Increased plasma VEGF expression is asso-ciated with the development of metastasis in HCC after TA-CE.

Radiofrequency ablation or microwave ablation combined with transcatheter arterial chemoembolization in treatment of hepatocellular carcinoma by comparing with radiofrequency ablation alone

Objective：To compare radiofrequency ablation （RFA） or microwave ablation （MWA） and transcatheter arterial chemoembolization （TACE） with RFA or MWA monotherapy in hepatocellular carcinoma （HCC）.Methods：A prospective,randomized,controlled trial was conducted on 94 patients with HCC ≤7 cm at a single tertiary referral center from June 2008 to June 2010 at the Department of Hepatobiliary Surgery,the Second Affiliated Hospital of Southeast University.The patients were randomly assigned into the TACERFA or TACE-MWA （combined treatment group） and the RFA-alone or MWA-alone groups （control group）.The primary end point was overall survival.The secondary end point was recurrence-free survival,and the tertiary end point was adverse effects.Results：Until the time of censor,17 patients in the TACE-RFA or TACE-MWA group had died.The median follow-up time of the patients who were still alive for the TACE-RFA or TACE-MWA group was 47.5±11.3 months （range,29 to 62 months）.The 1-,3-and 5-year overall survival for the TACE-RFA or TACE-MWA group was 93.6％,68.1％ and 61.7％,respectively.Twenty-five patients in the RFA or MWA group had died.The median follow-up time of the patients who were still alive for the RFA or MWA group was 47.0±12.9 months （range,28 to 62 months）.The 1-,3-and 5-year overall survival for the RFA or MWA group was 85.1％,59.6％ and 44.7％,respectively.The patients in the TACE-RFA or TACE-MWA group had better overall survival than the RFA or MWA group [hazard ratio （HR）,0.526; 95％ confidence interval （95％ CO,0.334-0.823; P=0.002],and showed better recurrence-free survival than the RFA or MWA group （HR,0.582; 95％ CI,0.368-0.895; P=0.008）.Conclusions：RFA or MWA combined with TACE in the treatment of HCC ≤7 cm was superior to RFA or MWA alone in improving survival by reducing arterial and portal blood flow due to TACE with iodized oil before RFA.

Doxorubicin-eluting bead vs conventional transcatheter arterial chemoembolization for hepatocellular carcinoma before liver transplantation

AIM:To assess the possible effect of two different types of preoperative transcatheter arterial chemoembolization(TACE)on recurrence-free survival after liver transplantation(LT)in patients with hepatocellular carcinoma(HCC)and to analyze the effects of TACE on tumor histology.METHODS:We retrospectively analyzed the histological features of 130 HCC nodules in 63 native livers removed at transplantation.Patients who received any other type of treatment such as radiofrequency tumor ablation,percutaneous ethanol ablation or who were not treated at all were excluded.All patients in the present study were within the Milan Criteria at the last imaging findings before transplantation.Doxorubicineluting bead TACE(DEB-TACE)was performed in 22patients(38 nodules),and conventional TACE(c-TACE)in 16(25 nodules).Patients’and tumors’characteristics were retrospectively reviewed.We performed a pernodule analysis of the explanted livers to establish the mean percentage of necrosis of any nodule treated by TACE(conventional or DEB)and a per-patient analysis to establish the percentage of necrosis in the cumulative tumor area,including 21 nodules not reached by TACE.Inflammatory and fibrotic changes in the tissue surrounding the tumor nodule were analyzed and categorized as poor/absent,moderate and enhanced reaction.Uni-and multivariate analysis of risk factors for HCC-recurrence were performed.RESULTS:The number and diameter of the nodules,the time spent on the waiting list and the number of treatments were similar in the two groups.A trend towards higher appropriate response rates(necrosis≥90%)was observed in the DEB-TACE group(44.7%vs32.0%,P=0.2834).The mean percentage of necrosis in the cumulative tumor area was 58.8%±36.6%in the DEB-TACE group and 50.2%±38.1%in the c-TACE group(P=0.4856).Fibrotic and inflammatory reactions surrounding the tumor nodule were markedly more common in the DEB-TACE group(P<0.0001,for both the parameters).The three-year recurrence-free survival was higher in DEB-TACE-treated patients than in conventionally treated patients(87.4%vs 61.5%,P=0.0493).Other factors affecting recurrence-free survival included viable tumor beyond Milan Criteria on histopathological examination,the percentage of necrosis on CTA≤50%and a pre-transplant serum-fetoprotein level greater than 70 ng/mL.On multivariate analysis,the lack of treatment with DEB-TACE,high levels of-fetoprotein and viable tumor beyond Milan Criteria at histology examination were identified as independent predictors of tumor recurrence.CONCLUSION:DEB-TACE can effectively promote tumor necrosis and improves recurrence-free survival after LT in HCC.

A comparative study between Embosphere~ and conventional transcatheter arterial chemoembolization for treatment of unresectable liver metastasis from GIST

Objective：Transcatheter arterial chemoembolization （TACE） is a standard treatment for hepatocellular carcinoma （HCC） and/or some unresectable liver metastasis tumors.Hypervascular liver metastatic lesions such as metastasis from gastrointestinal stromal tumor （GIST） are an indication for transcatheter arterial embolization （TAE）.The purpose of this study was to evaluate the efficacy and safety of Embosphere（㊣）-TAE （Embo-TAE） in comparison with conventional TACE （cTACE） for the treatment of liver metastasis from GIST.Methods：A total of 45 patients who underwent TACE between Aug 2008 and Feb 2013 were enrolled.Patients with GIST who underwent TAE with Embosphere（㊣） （n=19） were compared with controls who received cTACE （n=26）.The primary end points were treatment response and treatment-related adverse events.The secondary end points were progression-free survival （PFS） and overall survival （OS）.Results：The treatment response of Embo-TAE group was significandy higher than that of the cTACE group （P＜0.001）.The PFS was significandy better in the Embosphere（㊣）-group than in the cTACE group （56.6 and 42.1 weeks,respectively; P=0.003）.However,there was no statistically significant difference in liver toxicity between the two groups （P＞0.05）.The median OS in the Embo-TAE group was longer than that in the cTACE group （74.0 weeks,95％ CI：68.2-79.8 vs.61.7 weeks,95％ CI：56.2-67.2 weeks） （unadjusted P=0.045）.The use of Embo-TAE significantly reduced the risk of death in patients with GIST with liver metastases according to the Cox proportonal hazards regression model [hazard ratio （HR）：0.149; 95％ CI：0.064-0.475].Conclusions：TAE with Embosphcre（㊣） showed better treatment response and delayed tumor progression compared with cTACE.There was no significant difference in treatment-related hepatic toxicities.EmboTAE thus appears to be a feasible and promising approach in the treatment of liver metastasis from GIST.

Clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization combined with radiotherapy in hilar cholangiocarcinoma

BACKGROUND Radical surgical resection is regarded as the best treatment for hepatic hilar cholangiocarcinoma. However, 60%-70% of patients have lost the chance of surgery at the time of diagnosis. Simple biliary stent or drainage tube placement may fail in a short time due to tumor invasion or overgrowth, bile accumulation, or biofilm formation. Effective palliative treatments to extend the effective drainage time are of great significance for improving the quality of life of patients and changing the prognosis of patients. AIM To investigate the clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization (TACE) combined with radiotherapy in hilar cholangiocarcinoma.METHODS A retrospective analysis was conducted on patients clinically diagnosed with hilar cholangiocarcinoma from June 2014 to January 2017 at the Liaoning Provincial Cancer Hospital. Patients were evaluated by specialists, and those who were not suitable for surgery or unwilling to undergo surgery and met the inclusion criteria were included in the study. There were a total of 72 patients (34 males and 38 females) with an average age of 59.9 years (range, 40-72 years). According to percutaneous transhepatic biliary angiography and the patients’ wishes, stent implantation or biliary drainage tube implantation was used to relieve biliary obstruction. The patients were divided into either a control group or a combined treatment group according to their follow-up treatment. The control group consisted of a total of 35 patients who received simple biliary drainage tube placement and biliary stent implantation (7 patients with bilateral stents and 6 with a unilateral stent) and 22 patients receiving biliary drainage tube placement alone. The combined treatment group received TACE and extracorporeal radiotherapy after biliary drainage or biliary stent implantation and consisted of a total of 37 patients, including 21 patients receiving combined treatment after biliary stent placement (14 patients with bilateral stents and 7 with a unilateral stent) and 16 undergoing combined therapy after implanting the biliary drainage tube. In the combination treatment group, the TACE chemotherapy regimen employed gemcitabine and cisplatin, and the embolic agent was iodized oil. A particular dose was determined according to the patient's body surface area and the tumor staining indicated by DSA. In vitro radiotherapy was performed with intensity-modulated radiotherapy or threedimensional conformal radiotherapy at an average dose of 48.3 Gy. Both groups were followed from stent implantation or drainage tube implantation until the patient quitted or died. The median length of follow-up observation was 13 mo. The differences in overall survival time and the effect of different jaundice reducing methods (single stent, double stent, or biliary drainage) on the patency time and survival time of biliary stents were compared between the two groups;the related factors affecting overall survival time were analyzed. RESULTS The median survival time of the control group was 10.5 mo;the median survival time of patients with biliary stent implantation and those with percutaneous biliary drainage was 9.6 mo and 11.4 mo, respectively, and there was no statistically significant difference between them. The median survival time of the combined treatment group was 20.0 mo, which was significantly higher than that of the control group (P < 0.05). Among patients in the combined treatment group, the median survival time of patients who underwent biliary stent implantation and those who accepted percutaneous biliary drainage before the combination therapy was 19.5 mo and 20.1 mo, respectively, and there was no significant difference between them. In the combination treatment group, the mean time of median stent patency was 15.6 mo, which was significantly higher than that of the control group (7.0 mo;P < 0.05). The independent factors affecting survival time included age, whether to receive combination therapy, percutaneous biliary drainage tube implantation, and Bismuth-Corlette classification as type IV. CONCLUSION Gemcitabine and cisplatin-based TACE combined with radiotherapy can prolong the survival of patients with hilar cholangiocarcinoma. Independent predictors of survival include selection of combination therapy, Bismuth-Corlette classification as type IV, selection of percutaneous biliary drainage tube implantation, and age.